Abstract 317: Physiologic Cardiac Hypertrophy in Mice Reduces mRNA Levels of Myostatin and Autophagy Genes
Myostatin and autophagy are involved in muscle growth regulation. However, there are few studies exploring their role in physiologic cardiac hypertrophy. We evaluated myostatin and autophagy in mice subjected to a swimming protocol to induce physiologic cardiac hypertrophy. Methods: Adult (8 weeks-old) male BALB/c mice (n=52) were divided in sedentary (S) and trained (T) groups, which were evaluated in 7 (S7 or T7, initial hypertrophy) and 28 (S28 or T28, stablished hypertrophy) days after the start of the protocol. Left ventricular/tibial length ratio (LV/TL) and cardiomyocyte diameter were used to assess cardiac hypertrophy. Gene expression was evaluated by RT-qPCR, while protein expression was analyzed by western blot. Bioinformatic analysis was performed by TargetScan to predict potential miRNAs’ targets and Genemania to create an interaction network between miRNAs and genes. All results were expressed as mean ± SEM and comparisons were performed using the Student T test. Results: Myocardial hypertrophy was confirmed in trained group both by the increase in LV/TL ratio in 28 days (13%, p=0.0001) and cardiomyocyte diameter in 7 days (20%, p=0.04) and 28 days (30%, p=0.002). There was a decrease in myostatin gene expression levels in T7 compared to S7 group (0.8 ± 0.1 vs 1.2 ± 0.1, p=0.01) without changes at day 28. However, there was no difference in mTOR phosphorylation at T7, although it was increased in T28 compared to S28 (397±95 vs 90±23 AU; p=0.02). Autophagic genes showed reduced expression levels in trained groups at both time points (reductions of 19% and 10% for Lc3, 22% and 11% for P62, 19% and 10% for Beclin1 in T7 and T28, respectively; p<0.05 for all analyses compared to sedentary groups), but there was no difference at protein level. Bioinformatics analysis showed that miR-30a, - 221, -27a/b and 208a/b are possible regulators of autophagic and myostatin genes. Conclusions: Taken together, reduced myostatin during initial hypertrophy and increased mTOR phosphorylation in the established hypertrophic phenotype might favor muscular growth and reduce basal autophagy. Candidate miRNAs identified through bioinformatic analysis might regulate this process, and should be further validated in this scenario.
Author Disclosures: G.H. Pinto: None. M.E. Andrades: None. C. Cohen: None. N.C. Martinelli: None. S.A.T. Leitão: None. M.R. Mendoza: None. L.E.P. Rohde: None. N.O. Clausell: None. A. Biolo: None.
- © 2015 by American Heart Association, Inc.